Apparatus and process for removing substances from pre-filled containers

ABSTRACT

A system (10) for removing a pipettable substance from a pre-filled container (20), which is closed off by a lid (30) having at least one opening area (40), comprises an opening tool (100) having a tube (110), which has a cross-section corresponding substantially to the shape of the opening area and which comprises at a distal end (120) an endpiece (140) extending substantially obliquely relative to the longitudinal axis of the tube, which moves a part of the lid (30) located inside the opening area (40) towards the container when the opening tool is applied, so as to form an opening in the lid, and a point of attack (150) for a transporting tool (200). The opening tool (100) is designed to remain on the container (20) after use. Moreover, the system comprises a transporting tool (200) for moving the opening tool (100) through the lid, and a cannula (250), which is adapted to be inserted over at least part of its length through the tube (110) into the interior of the container (20), in the position of use of the opening tool (100), and one end of which can be connected to a suction device (300) for sucking a pipettable substance out of the interior of the container (20).

This application is a divisional of U.S. application Ser. No.12/673,758, filed Mar. 22, 2011, which is a § 371 National StageApplication of PCT/EP2008/060810, filed Aug. 18, 2008, which claimspriority to European Application 07016192.2, filed Aug. 17, 2007 andEuropean Application 07018725.7, filed Sep. 24, 2007, the contents ofwhich are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to an apparatus for removing substancesfrom pre-filled containers. The apparatus is suitable for example forapplications in biochemistry, molecular genetics, microbiology, medicaldiagnostics or forensic medicine.

Description of Related Art

In numerous technical fields such as chemistry, biology, biochemistry,biotechnology, medicine or environmental technology it is necessary toanalyse, separate, process or react materials containing biologicaltarget molecules (e.g. pourable biological samples). For this purposethe liquids or materials are filtered, cooled, heated, broken down intotheir components, washed or pipetted by various methods and/or treatedby other methods. It is often necessary to go through a long and complexsequence of processing steps in order to prepare the biologicalmaterial. During processing, various reagents are added. Depending onthe nature of the analysis or the preparation of the sample, differentcombinations reagents are used during the process. Particularly forlarger quantities of sample the processing is typically automated.Usually, the reagents needed for the processing are held in pre-filledcontainers and placed by an operator in an apparatus for automaticsample processing. In order to remove the reagents the apparatus isprovided with means for opening the containers—if these have not alreadybeen opened during the loading of the apparatus—and for controlledremoval. The opening and removal may be done by the same tool, forexample by pushing a cannula through a perforatable top of the containerand then sucking out the reagent using an external suction device.

A number of variants are known for removing pipettable substances frompre-filled containers. However, the prior art leaves plenty of room forimprovement. The objective of the present invention is therefore toconstruct an apparatus of this kind with a view to improving theprocessing efficiency and economy.

SUMMARY OF THE INVENTION

In one aspect the invention relates to a system for removing apipettable substance from a pre-filled container sealed off with a tophaving at least one opening area, comprising an opening tool with a tubewhich has a cross-section corresponding substantially to the shape ofthe opening area and which comprises at a distal end a closure extendingsubstantially at an angle relative to the longitudinal axis of the tube,which moves a part of the top located inside the opening area towardsthe container when the opening tool is applied, so as to form an openingin the top. In addition, the opening tool has a point of attack for atransporting tool, the opening tool being designed to remain on thecontainer after use, a transporting tool for moving the opening toolthrough the top, and a cannula which is adapted to be inserted over atleast part of its length through the tube into the interior of thecontainer, in the state of use of the opening tool, and one end of whichcan be connected to a suction device for sucking a pipettable substanceout of the interior of the container.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

Typically the opening area is substantially of a shape selected fromamong a circle, ellipse or polygon. It is also typically characterisedby one or more of the features selected from the follow ing group:

-   -   the opening area has a substantially lesser material thickness        than the top,    -   the opening area consists of a different material from the top,    -   the opening area is confined by a boundary region which        substantially has a lesser material thickness than the top, the        boundary region typically having areas of different material        thickness,    -   the opening area is confined by a boundary region of greater        material thickness than the top.

Typically, the opening tool comprises at least one positioning elementfor exact positioning on the container, selected from among a pin, hole,slot, groove and ridge.

Typically, the inclined endpiece of the tube of the opening tool has apoint at its distal end and has at least two different angles α relativeto the longitudinal axis of the tube over the area from its dorsal endto its distal end. Typically the angle α of the slant of the endpiece ofthe tube relative to the longitudinal axis of the tube in the region ofthe distal end of the endpiece is substantially smaller than in otherareas of the endpiece.

Typically, one end of the tube ensures a friction-locked engagement ofthe tube in the top of the container with the opening tool in itsapplied position, typically by a construction in the shape of a cone.

Typically, a plurality of tubes are arranged in an m×n matrix andconnected by a common element. Typically, a spatial direction defined bya perpendicular to the main plane of the inclined endpiece of the tubeis different in at least two of the tubes.

In another aspect the invention relates to a container for providingpipettable substances which comprises a plurality of similar ordifferently shaped chambers each having at least one opening and atleast one top for closing off the openings, and cone-like guides formedin the at least one top.

Typically, the container comprises a positioning element selected fromamong the group comprising a pin, a hole, a slot, a groove and a ridge.

Typically, the at least one top of the container is provided with atleast one opening area.

Typically, the opening area of the top of the container essentially hasa shape selected from among a circle, ellipse and polygon. The openingarea is moreover typically characterised by one or more of the featuresselected from the following group:

-   -   the opening area has a substantially lesser material thickness        than the top,    -   the opening area consists of a different material from the top,    -   the opening area is confined by a boundary region which        substantially has a lesser material thickness than the top, the        boundary region typically having areas of different material        thickness,    -   the opening area is confined by a boundary region of greater        material thickness than the top.

Typically the container is filled with substantially all the substancesrequired for a predetermined process, particularly for processing,purifying and/or analysing materials containing biological targetmolecules.

In another aspect the invention relates to an opening tool for apre-filled container closed off by a top which has at least one openingarea, the opening tool comprising a tube which has a cross-sectioncorresponding substantially to the shape of the opening area and at adistal end an endpiece extending substantially at an angle relative tothe longitudinal axis of the tube, which moves a part of the top locatedinside the opening area toward the container when the opening tool isapplied so as to make an opening in the top in this way, the inclinedendpiece having a point at its distal end and having at least twodifferent angles α relative to the longitudinal axis of the tube overthe area from its dorsal end to its distal end.

Typically, the angle ca of the slant of the endpiece of the tuberelative to the longitudinal axis of the tube in the region of thedistal end of the endpiece is substantially smaller than in other areasof the endpiece.

Typically, a tube of the opening tool comprises a retaining element forfixing the opening tool to the container, typically in the form of ashoulder or groove that at least partly encircles the tube.

Typically, one end of the tube ensures a friction-locked engagement ofthe tube in the top with the opening tool in its applied position, thetube typically being in the shape of a cone over at least part of itslength.

Typically a plurality of tubes of the opening tool are arranged in anm×n matrix and connected by a common element. Typically, a spatialdirection defined by a perpendicular to the main plane of the inclinedendpiece of the tube is different in at least two of the tubes.

In another aspect the invention relates to a process for removing apipettable substance from a pre-filled container, comprising the stepsof:

-   -   a) providing a system according to the invention and a container        according to the invention,    -   b) automated or manual application of an opening tool according        to the invention to a top of the container,    -   c) moving the opening tool through the top of the container so        that a tube of the opening tool at least partly opens an opening        area in the top of the container and the tube penetrates into        the interior of the container, over at least part of its length,        and is fixed therein,    -   d) positioning a pipetting tool in a position above a        through-opening in the opening tool and lowering the pipetting        tool into the through-opening and into the tube below, until at        least part of the pipetting tool projects from the distal end of        the tube into the substance that is to be removed,    -   e) sucking up a pipettable substance contained in the container        through the pipetting tool by means of a suction device        connected thereto.

Typically the process comprises an additional step f) in the form of thetotal withdrawal of the cannula from the opening tool.

Typically, steps d) to f) are repeated several times, using the same ordifferent cannulas.

Typically, the movement in step c) is accompanied by the engagement ofpositioning elements between the container and the opening tool, whichare selected from among the group comprising pin-hole, pin-slot andgroove-ridge.

Typically steps d) to f) are carried out using a plurality of pipettingtools at the same time.

Typically the container used in the process has a number of separatechambers, each of which has an associated opening area in a top.Typically in step c) a plurality of tubes open a plurality of openingareas at least in part as the opening tool is moved.

Typically the process comprises a further step g) in which the containerwith the opening tool applied is closed off by means of a cover arrangedon the opening tool.

Typically in step b) the opening tool is centred on the top by means oftypically conically shaped guides.

In view of the above remarks a system according to claim 1, a containeraccording to claim 10, an opening tool according to claim 16 and aprocess according to claim 22 are provided.

The details of the invention will be explained more fully hereinafterwith reference to various embodiments, referring to the accompanyingdrawings, wherein:

FIGS. 1a-1b show schematic views of a system according to one embodiment

FIG. 2a shows a perspective view of a container without an opening toolaccording to one embodiment

FIG. 2b shows a perspective view of a container with an opening toolaccording to one embodiment

FIGS. 3a-3b show a perspective view and lateral cross-sectional view ofa top according to one embodiment

FIGS. 4a-4b show a perspective view and cross-sectional view of anopening tool according to one embodiment

FIGS. 5a-5b show cross-sectional views of a container with a top andopening tool according to one embodiment, before and after the openingprocess

FIG. 6 is a schematic plan view of an opening area of a top according toone embodiment

FIGS. 7a-7d are perspective views and a cross-sectional view of tubes ofan opening tool according to embodiments

In the following description of various embodiments of the presentinvention, functionally similar features of the different embodimentshave been given the same reference numerals.

FIG. 1a schematically shows a preferred embodiment of a system accordingto the present invention. A container (20) pre-filled with pipettablesubstances (reagents) is closed off by a top (30). This top has at leastone opening area (40). An opening tool (100) comprises at least one tube(110) which has a cross-section corresponding substantially to the shapeof the opening area and at its distal end (120) an endpiece (140)(hereinafter also referred to as the cutting edge) that extendssubstantially obliquely relatively to the longitudinal axis of the tube.To prepare for the application of the opening tool the latter is placedon the top of the container so that the endpiece of the tube (110) isresting on the opening area. In order to open it the opening tool andthe container (20) are pressed together, typically by means of atransporting tool (200), which engages on at least one point of attack(150) on the opening tool and/or on the container. Typical embodimentsof a transporting tool of this kind are known to the skilled man.

In particular, the opening tool (100) and/or the container (20) may eachbe equipped with at least one positioning element for accuratepositioning on the transporting tool (200). Typically, elements areselected from a group comprising pins, holes, slots, grooves and ridges.One or more positioning elements of the transporting tool (200) engage,during the pressing process, with a mating positioning element, as acounterpart, which is provided on the container and/or on the top (30).Corresponding possible pairs are pin and hole, pin and slot, groove andridge or pin and groove, while combinations of other elements may alsobe regarded as falling within the scope of the invention.

During the opening, a part of the top (30) located inside the openingarea (40) is moved by the pressure of the endpiece of the tube towardsthe container (20) and in this way an opening is made in the top (30).FIGS. 3a and 3b show a preferred embodiment of the top. At the same timethe tube penetrates through the opening into the interior of thecontainer. The opening tool (100) remains on the container (20) afterthe opening process described above.

A stable positioning of the tool in the container can be ensured by anumber of different methods. In a preferred embodiment the opening toollodges in the top (30) of the container (20) by mechanical frictionalengagement. Another variant comprises a retaining element, e.g. ashoulder (175) or groove running around the outside of the tube andengaging with the top (30) of the container (20). The shoulder and otherdetails are not shown in FIGS. 1a and 1b for reasons of clarity; anillustration of the shoulder (175) by way of example is to be found inFIGS. 7c and 7d . The shoulder or groove may extend continuously or overonly parts of the outside of the tube.

In order to remove the pre-filled substance a pipetting tool (250) isthen inserted, at least over part of its length, through athrough-opening (190) in the tube (110) of the opening tool into theinterior of the container (20) until at least part of the pipetting toolprotrudes out of the distal (lower) end (120) of the tube into thesubstance that is to be removed. The pipetting tool is connected to asuction device (300) which is designed to suck up a pipettable substancefrom the interior of the container (20). The pipetting tool can beinserted both by means of actuators, which are typically operated byautomatic control, and manually, and this also applies to laterwithdrawal of the pipetting tool from the container or tube. FIG. 1bschematically shows the system with the opening tool (100) applied and apipetting tool (250) which has been inserted in the container.

Using the pipetting tool, the end of which protrudes into the substanceto be pipetted in the pre-filled container (20), the substance is thenremoved from the container by means of the suction device (300). Eithersome or all of the contents of the container can be removed in oneoperation. For example, using the pipetting tool, some of the contentscan be removed, the pipetting tool can be withdrawn completely from thecontainer (e.g. retracted) and moved into a parking position, forexample. At a later time more of the contents of the container can thenbe removed using the same or a different pipetting tool.

The advantage of the present invention over known systems in the priorart is that the process of opening the top and removing the pipettablesubstance are carried out separately. This prevents the sharp end of thepipetting tool, which is used to pierce the top in systems known fromthe prior art, from becoming blocked or damaged. At the same time thedemands made of the mechanical stability of the pipetting tool arereduced as it does not have to transmit the force needed to open thetop. Moreover, by separating the opening tool and the pipetting tool itis also possible to detect the level of pipettable substance remainingin the container through the opening, as the opening is still there evenafter the pipetting tool has been withdrawn. Other embodiments of theinvention relate to further features of the opening tool and top whichallow easier, reliable opening.

If the pipetting tool has been removed completely from the containerafter one or more removal processes and no further substances are to beremoved at this stage, the container (20) with the opening tool (100)placed thereon can optionally be resealed by means of a cover in orderto prevent any contamination or evaporation of the pre-filledsubstances. The cover is arranged on the opening tool. The nature of thecover is not particularly restricted and there are numerous possibleembodiments known from the prior art such as foils, covers made offlexible or rigid materials such as plastics, metal or the like. Thecover may be intended for both single and repeated use.

FIG. 2a shows a container (20) according to one embodiment of theinvention. The container may comprise a plurality of chambers or inserts(70) which are constructed to be separate from one another, of identicalor different shapes, each having at least one opening. In the Figure, achamber (70) is schematically represented by dotted lines, by way ofexample. In a typical application of the invention, the container (20)comprises several (in this case seven) chambers or inserts (70) whichare filled with substantially all the substances required for aparticular processing operation, particularly for processing, separatingand/or analysing a material containing a biological target molecule.These include, for example, one or more lysing solutions, washingsolutions, eluting solutions, buffers, binding solutions, separatingmaterials in pipettable form such as suspensions of magnetic beads,enzymes, probes, markers, starting materials for downstream applicationssuch as PCR, arrays and/or assays and the like.

In the embodiment described, the chambers or inserts (70) are typicallyprovided with the lids (30) described in more detail hereinafter.Besides the chambers, the contents of which are removed using theprocess or system according to the invention, the container may comprisefurther chambers and/or inserts (65, 75), which typically also containmaterials for carrying out the planned processes, but wherein thecontents are not removed by means of the process or system according tothe invention. Thus, some of the materials mentioned above by way ofexample may be located in the chambers or inserts (70), whereas otherrequired substances are advantageously introduced into the remainingchambers and/or inserts of the container. It is particularlyadvantageous if the one or more lysing solutions, washing solutions,eluting solutions, binding solutions and/or buffers are contained in thechambers (70).

The use of inserts that can be introduced into the container and takenout of it again has the advantage that materials requiring specialtreatment, such as enzymes which have to be refrigerated, or suspensionsthat have to be homogenised again immediately before use, can undergotheir special treatment independently of the other materials and thecontainer as a whole.

The chambers in the embodiment shown in FIG. 2b are each provided with atop (30) to which the opening tool (100) is applied. In the figure achamber (70) is schematically shown by dotted lines, by way of example.The through-openings (190) made by the opening tool allow the pipettingtool to be introduced into the chamber or insert (70). FIG. 2b alsoshows a cover (350), which is applied only to one of the lids, by way ofexample. The cover may advantageously be used repeatedly and istypically made from a resilient plastics material.

FIG. 3a shows a perspective view of a top (30) for the container (70)according to one embodiment. FIG. 3b shows a cross-section through thistop (30). The typically conically shaped guides (35) over the openingareas (40) advantageously have a guide function for the tubes (110) ofthe opening tool (100), so that the tool is centred as it is applied tothe top. One or more opening areas (40) in the top (30) have associatedwith them one or more underlying chambers (70) of the container (20). Inthe embodiment shown, four opening areas are provided for one chamber.Depending on the design, the same substance can be taken from onechamber and/or different or identical substances can be taken from aplurality of chambers using a plurality of pipetting tools at the sametime through several openings in the top. In the case of a plurality ofpipetting tools, corresponding adaptation of the suction device (300)may be necessary, or a number of suction devices may be used.

FIG. 4a shows a preferred embodiment of the opening tool (100) whichcomprises a plurality of tubes (110) arranged in an m×n matrix andconnected by an element (180). The tubes (110) of the opening tool aretypically at different angular positions relative to their longitudinalaxes. In other words, the spatial direction defined by the perpendicularto a main plane of the slanting endpiece (140) of the tube (110) differsfrom one individual tube to another. By the main plane is meant theplane which, in the understanding of a skilled man, is most suitable forrepresenting the direction of the endpiece.

Typically the angular positions of the perpendiculars between theindividual tubes differ by multiples of 900, giving four differentpossible angular positions. This ensures guiding and centering of theopening tool when it is applied to or placed on the top (30) by means oftypically conically shaped guides (35).

FIG. 4b shows a cross section through the opening tool of FIG. 4a alongthe stretch A-A, wherein the different sectional profiles of the tubesare shown, which are a result of the different angular positions.

In one embodiment of the invention the tube (110) of the opening tool(100) may have a cross sectional shape which is other than circular,such as (as non-restrictive examples) the cross sectional shapes of anellipse or polygon or any desired variations. In addition, the tube(110) may have a structure which is only substantially tubular butdeviates from a tubular shape. These might include for example missingsegments or differently shaped openings in the wall structure.

FIG. 5a shows a container (20) with its associated top (30) and openingtool (100) placed thereon, according to a preferred embodiment. The tipsof the tubes (110) are located on the opening areas (40) of the top(30). Technical measures may be taken to prevent the positioned openingtool from accidentally damaging or perforating the opening areas of thetop. The conical guides (35) centre the tubes (110) and hence theopening tool (100) in relation to the top. FIG. 5b shows the positionafter the opening tool (100) has been pressed through the top (30). Theopening areas (40) cut out by the cutting edges (140) are not shown inFIG. 5 b.

As already shown, as the opening tool is moved or pressed in thedirection of the opening areas, a part of the top (30) located insidethe opening area (40) is moved in the direction of the container and inthis way an opening is made in the top. The slanting endpiece (140) ofthe tube (110), acting as a kind of cutting edge, exerts a force on theopening area. In one embodiment of the invention the entire opening area(40) has a substantially lesser material thickness than the remainder ofthe top (30), in order to facilitate the opening process. In anotherembodiment the opening area is made from a different, typically softermaterial than the rest of the top, in order to assist with cutting open,a process which can be carried out for example using a 2C (2 component)injection moulding process known in the art. The opening area may alsobe in the form of a foil or film.

FIG. 6 shows a detail of a top (30) of the container (20) according to apreferred embodiment of the invention. The opening area (40) is confinedby a boundary region (50). The boundary region acts as a kind offrangible point or weakened point, along which the connection betweenthe opening area and the top is to be broken by means of the cuttingedge. For this purpose the boundary region is designed so that easyseparation is guaranteed using the cutting edge. This can be achieved invarious ways.

In a preferred variant the boundary region is constructed so as to havea different, typically lesser material thickness than the rest of thetop (30). In another embodiment the boundary region (50) itself hasregions of different material thickness. As a non-restrictive example,in a circular boundary region (50), half of the circle may have amaterial thickness corresponding to a quarter of the thickness of thesurrounding top, while the other half has a material thickness of 70% ofthat of the surrounding top.

In another embodiment the boundary region is made of a differentmaterial from the rest of the top, which may be achieved for exampleusing a 2C injection moulding process known in the art. The boundaryregion may also be in the form of a foil or film, for example.

By bounding the opening area with a region of lesser material thicknessit is easier to open using the means according to the invention. In theembodiment mentioned above with a variable thickness of the boundaryregion (50), an additional effect is achieved. The region of lesserthickness allows easy initial penetration or cutting by means of theendpiece (140) of the tube (110). As the tube increasingly penetratesinto the container the boundary region (50) is cut through more and moreby the slanting endpiece (140). It is desirable that the opening areashould not be totally severed from the rest of the top as otherwise thesevered part could fall into the container. This could lead to problemsduring pipetting if the severed part of the top were to lie in front ofthe opening of the pipetting tool. The rather thicker region of theboundary region helps to prevent the boundary region from being severedcompletely. As a result the cut away part of the opening area remainsattached to the rest of the top at this point and does not fall into thecontainer (20).

The objective of opening the top with minimum force and preventing totalsevering of the opening area, as already described above, is alsoachieved by means of the following embodiments of the invention. Theamount of force required is particularly great if a number of openingareas are to be opened simultaneously and if the top is firmly attachedto the container, e.g. by welding. In addition, considerable forces arerequired when using conventional closure materials such as polyethyleneto form the top.

FIG. 7a shows a tube (110) of the opening tool according to oneembodiment of the invention. The tube (110) has a dorsal end (125) and adistal end (120). The oblique endpiece (140) (cutting edge) also has adorsal end (160) and a distal end (170). In this embodiment the angle ofthe slant (140) is constant.

FIG. 7b shows an embodiment of the invention in side elevation, whereinthe slant of the endpiece (140) of the tube (110) has at least twodifferent angles α relative to the longitudinal axis of the tube, in thearea from the dorsal end (160) to the distal end (170) of the endpiece.Typically the endpiece is constructed so that the smaller angle is inthe region of the distal end (170) and the larger angle is in the regionof the dorsal end (160). This allows cutting or penetration to takeplace with reduced application of force compared with an endpiece havinga constant slant angle. As a result of the larger angle at the dorsalend (160) the cutting action of the slanting endpiece (140) of the tubein this region is reduced, as a result of which part of the boundaryregion (50) is not cut through, if the dimensions are suitably chosen.The endpiece (140) of the tube thus acts not as a cutting edge but as apressing edge at this point, the part of the opening area which hasalready been cut away being pressed towards the interior of thecontainer.

FIG. 7c shows a preferred embodiment of the invention in side elevation,wherein the annular configuration is particularly advantageous for thepurpose outlined above. For manufacturing or other reasons it may beexpedient for the angle of the slant to be somewhat larger over a shortsection in the immediate vicinity of the distal end (170) than in theconfiguration described above. This is considered to be within the scopeof the invention and is illustrated in FIG. 7c (enlargement of the slantangle underneath reference numeral 170).

FIG. 7d shows another preferred embodiment of the invention as across-sectional view through the tube (110). At the distal end (170) isformed a point (135) to assist with the incision or the beginning of theseparation of the opening area or the boundary region. The point (135)makes it possible to make an incision or penetrate the boundary regionwith reduced application of force compared with an endpiece that doesnot have a corresponding point. Advantageously, the point (135) iscombined with one of the previous embodiments (from FIG. 7b , FIG. 7c ),as shown in FIG. 7d . However, it is also possible according to theinvention to combine the embodiment with a point having an endpiece withfor example a constant slant angle α.

It is also possible to have embodiments according to the invention inwhich the opening area is detached completely from the remainder of thetop. The top may either fall into the container or be removed from thecontainer by other means.

In a preferred embodiment a dorsal end (125) of the tube (110) ensuresthat the end of the tube is lodged by frictional engagement in the top(30) of the container (20) when the opening tool (100) is in the appliedposition. For this purpose the upper end of the tube is slightly conicalin shape, typically with an angle of about 0.5 to 5°, more typicallyabout 0.7 to 40 and most typically about 1 to 3°. This cone serves anumber of purposes. It smoothes out any unevenness in the cuttingcontour produced by the cutting edge and occurring during the incisioninto the opening area, by somewhat expanding the cutting contour. Inthis way the tube (110) or the opening tool (100) simultaneously forms aseal with the top (30) of the container (20), which at least partlyprevents or reduces evaporation in the case of volatile reagents such asalcohol. Finally, the frictional engagement provides a stable mechanicalfit of the tube in the top or container, with the result that there isno need for the positioning elements or similar elements for engagementor the like briefly described above.

If even greater stability is required compared with the friction-lockedfit described above, the opening tool (100) may be equipped with atleast one positioning element for accurately positioning it on thecontainer (20). Typically, elements are selected from a group comprisingpins, holes, slots, grooves and ridges. During the pressing action thepositioning element engages with a mating positioning element as acounterpart which is provided on the container or on the top (30).Corresponding possible pairs consist of a pin and hole, pin and slot,groove and ridge or pin and groove, although combinations of otherelements may also be taken into consideration within the scope of theinvention.

The invention is also directed to an apparatus for carrying out theprocesses disclosed and comprises apparatus components for performingeach of the process steps described. These process steps may be carriedout using hardware components, a computer programmed with suitablesoftware or any combination of the two, or by any other means. Inaddition, the invention is also directed to processes by which theapparatus described is operated. It comprises process steps forperforming each function of the apparatus.

The invention claimed is:
 1. A process for removing a pipettablesubstance from a pre-filled container, comprising the steps of: a)providing a container and a system for removing a pipettable substancefrom a pre-filled container covered by a top having an opening area,said system comprising an opening tool, comprising (i) a tube having across-section substantially corresponding to a shape of the opening areaand at a distal end, an endpiece extending substantially at an anglerelative to a longitudinal axis of the tube, and configured to move apart of the top located inside the opening area toward the containerwhen the opening tool is applied, thereby making an opening in the top,(ii) a point of attack for a transporting tool, the opening tool beingdesigned to remain on the container after use, a transporting tool formoving the opening tool through the top, a pipetting tool adapted to beinserted over at least part of a length thereof through the tube into aninterior of the container, in a position of use of the opening tool, andone end of which can be connected to a suction device for sucking apipettable substance out of the interior of the container, b) automatedor manual application of an opening tool to a top of the container, c)moving the opening tool through the top of the container by means of atransporting tool so that a tube of the opening tool at least partlyopens an opening area in the top of the container and the tubepenetrates into an interior of the container, over at least part of itslength, and is fixed therein, d) positioning a pipetting tool in aposition above a through-opening in the opening tool and lowering thepipetting tool into the through-opening and into the tube below, untilat least part of the pipetting tool projects from a distal end of thetube into a substance that is to be removed, e) sucking up a pipettablesubstance contained in the container through the pipetting tool by meansof a suction device connected thereto; wherein the container isconfigured to hold pipettable substances and comprises: a plurality ofchambers, each chamber having an opening area, wherein the plurality ofopening areas are arranged in rows and columns, a plurality of tops,wherein each top is configured to cover a row or a column of chamberopening areas, each top comprises a plurality of cone-shaped guides, andeach cone-shaped guide is disposed over the surface of its respectiveopening area, and wherein the opening area is confined by a boundaryregion having a variable thickness, wherein an opening is made in thetop when a part of a top located in the opening area is moved by aslanting endpiece of a tube moving towards the container.
 2. The processaccording to claim 1, further comprising f) total withdrawal of thepipetting tool from the opening tool.
 3. The process according to claim2, wherein d) to f) are repeated several times, using the same ordifferent pipetting tools.
 4. The process according to claim 1, whereinthe movement in c) is accompanied by the engagement of positioningelements between the container and/or the opening tool and thetransporting tool, which are selected from among the group consisting ofpin-hole, pin-slot and groove-ridge.
 5. The process according to claim1, wherein d) to f) are carried out using a plurality of pipetting toolsat the same time.
 6. The process according to claim 1, wherein theopening tool comprises a plurality of tubes that open the plurality oftubes open a plurality of opening areas at least in part as the openingtool is moved.
 7. The process according to claim 1, further comprising:g) closing off the container with the opening tool applied by means of acover arranged on the opening tool.
 8. The process according to claim 1,wherein in b) the opening tool is centred on the top.